Qiu Jian, Li Guo-Wei, Sui Yan-Fang, Song Hong-Ping, Si Shao-Yan, Ge Wei
Department of General Surgery, The Second Hospital of Xioan Jiaotong University, Xioan 710004, Shaanxi Province, China.
World J Gastroenterol. 2006 Jan 21;12(3):473-8. doi: 10.3748/wjg.v12.i3.473.
To study whether heat-shocked tumor cells could enhance the effect of tumor cell lysate-pulsed dendritic cells (DCs) in evoking anti-tumor immune response in vivo.
Mouse undifferentiated colon cancer cells (CT-26) were heated at 42 degrees Celsius for 1 h and then frozen-thawed. The bone marrow-derived DCs pulsed with heat-shocked CT-26 cell lysate (HSCT-26 DCs) were recruited to immunize syngeneic naive BALB/c mice. The cytotoxic activity of tumor specific cytotoxic T lymphocytes (CTLs) in mouse spleen was evaluated by IFN-enzyme-linked immunospot (ELISpot) and LDH release assay. The immunoprophylactic effects induced by HSCT-26 DCs in mouse colon cancer model were compared to those induced by single CT-26 cell lysate-pulsed DCs (CT-26 DCs) on tumor volume, peritoneal metastasis and survival time of the mice.
Heat-treated CT-26 cells showed a higher hsp70 protein expression. Heat-shocked CT-26 cell lysate pulsing elevated the co-stimulatory and MHC-II molecule expression of bone marrow-derived DCs as well as interleukin-12 p70 secretion. The IFN-gamma secreting CTLs induced by HSCT-26 DCs were significantly more than those induced by CT-26 DCs (P=0.002). The former CTLs' specific cytotoxic activity was higher than the latter CTLs' at a serial E/T ratio of 10:1, 20:1, and 40:1. Mouse colon cancer model showed that the tumor volume of HSCT-26 DC vaccination group was smaller than that of CT-26 DC vaccination group on tumor volume though there was no statistical difference between them (24 mm3 vs 8 mm3, P=0.480). The median survival time of mice immunized with HSCT-26 DCs was longer than that of those immunized with CT-26 DCs (57 d vs 43 d, P=0.0384).
Heat-shocked tumor cell lysate-pulsed DCs can evoke anti-tumor immune response in vivo effectively and serve as a novel DC-based tumor vaccine.
研究热休克肿瘤细胞是否能增强肿瘤细胞裂解物脉冲树突状细胞（DCs）在体内激发抗肿瘤免疫反应的效果。
将小鼠未分化结肠癌细胞（CT-26）在42摄氏度加热1小时，然后冻融。用热休克CT-26细胞裂解物脉冲的骨髓来源DCs（HSCT-26 DCs）用于免疫同基因未致敏的BALB/c小鼠。通过IFN-酶联免疫斑点法（ELISpot）和乳酸脱氢酶释放试验评估小鼠脾脏中肿瘤特异性细胞毒性T淋巴细胞（CTLs）的细胞毒性活性。在小鼠结肠癌模型中，比较HSCT-26 DCs诱导的免疫预防效果与单一CT-26细胞裂解物脉冲DCs（CT-26 DCs）诱导的免疫预防效果对小鼠肿瘤体积、腹膜转移和生存时间的影响。
热处理的CT-26细胞显示出更高的hsp70蛋白表达。热休克CT-26细胞裂解物脉冲提高了骨髓来源DCs的共刺激分子和MHC-II分子表达以及白细胞介素-12 p70分泌。HSCT-26 DCs诱导的分泌IFN-γ的CTLs明显多于CT-26 DCs诱导的（P = 0.002）。在10:1、20:1和40:1的系列E/T比下，前者CTLs的特异性细胞毒性活性高于后者CTLs。小鼠结肠癌模型显示，HSCT-26 DC疫苗接种组的肿瘤体积虽小于CT-26 DC疫苗接种组，但两者之间无统计学差异（24立方毫米对8立方毫米，P = 0.480）。用HSCT-26 DCs免疫的小鼠的中位生存时间长于用CT-26 DCs免疫的小鼠（57天对43天，P = 0.0384）。
热休克肿瘤细胞裂解物脉冲DCs能在体内有效激发抗肿瘤免疫反应，可作为一种新型的基于DCs的肿瘤疫苗。
